The goal of this Specialized Program of Research Excellence (SPORE) in pancreas cancer is to translate outstanding hypothesis-driven basic research into clinical treatment that saves lives. Pancreatic cancer is a devastating cancer that kills patients not just because it may be extremely aggressive but also because it is diagnosed late. This SPORE is a unique collaboration between Georgetown University, Geisinger Health System and INDIVUMED a German Research Institute with a German hospital consortium that brings together an outstanding academic institution, a large regional healthcare system and a German basic and clinical research system to address the biology of pancreatic cancer and clinical care. Project 1 focuses on inhibition of pleiotrophin, a novel heparin-binding growth factor that promotes invasion and metastasis in pancreatic cancer. Project 2 focuses on the role of neuregulins and pleiotrophin in an established model of neuron:tumor cell interaction with the goal of developing methods to block neural invasion by malignant pancreas cells that may ultimately aid in disease palliation. Project 3 focuses on recent findings that inhibition of the nuclear receptor coactivator AIB1 within pancreas cancer cells and adjacent endothelium may block signaling from multiple growth factors to enhance apoptosis. The activation of the ras/MAP kinase pathway that occurs in up to 90% of pancreas cancer is the focus for novel approaches to radiation sensitization in Proiect 4. Investigators at Georgetown have developed a rafl antisense inhibitor that is already in Phase I trial and have developed other molecular targets in the pathway that are complementary. In addition, this SPORE is developing the infrastructure and resources to acquire tissues and bodily fluids from patients (Pancreatic Tumor Bank and Serum Detection & Molecular Identification Cores) with an expected 120 curative resections a year. The SPORE will utilize a biostatistical core to insure that all projects have appropriate designs, methods of analysis, and an integrated database for reporting patient outcomes. Further, the SPORE will support developmental projects designed to generate new knowledge and approaches to early detection and promote the development of career tracks dedicated to translational research in pancreatic cancer. This SPORE is also establishing interactions with SPOREs in other institutions as well as with other NCI- and NIH-funded programs to promote the aggressive development of novel therapies for the control of pancreas cancer